Needleless injection device components, systems, and methods

ABSTRACT

A high-pressure fluid injection system, which includes a rechargeable injection chamber with a proximal end, a distal end, and an internal opening extending from the proximal end to the distal end, a plunger slideably engaged with the internal opening of the injection chamber, an injection tube extending from the distal end of the injection chamber and in fluidic communication with the internal opening of the injection chamber, and a check valve between the proximal and distal ends of the injection chamber. The internal opening includes a high-pressure zone adjacent to the check valve and having a first diameter, and a low-pressure zone proximal to the high-pressure zone and having a second diameter that is larger than the first diameter.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a CIP of PCT/US2009/006382, filed Dec. 4,2009, by AMS Research Corporation, entitled, DEVICES, SYSTEMS ANDMETHODS FOR DELIVERING FLUID TO TISSUE, which in turn claims priority toU.S. Provisional Application No. 61/120,101, filed Dec. 5, 2008,entitled INJECTION VOLUME CONTROL USING ONE OR MORE ROTATING, STEPPEDSTOPS; U.S. Provisional Application No. 61/120,163, filed Dec. 5, 2008,entitled MEANS OF REDUCING JET INJECTION RESPONSE TIME; and U.S.Provisional Application No. 61/122,884, filed Dec. 16, 2008, entitledMEANS OF AUTOMATING BALLOON INFLATION BY VOLUME OR PRESSURE CONTROL. Thepresent application also claims priority under 35 U.S.C. §119(e) to U.S.Provisional Application No. 61/226,906, filed Jul. 20, 2009, entitled,HIGH-PRESSURE INJECTION CATHETER SYSTEM HAVING STEPPED DOSAGE CONTROL;and U.S. Provisional Application No. 61/226,913, filed Jul. 20, 2009,entitled, HIGH-PRESSURE INJECTION CATHETER SYSTEM WITH RECHARGEABLEINJECTION CHAMBER. Each of these above-listed applications isincorporated herein by reference in its entirety.

TECHNICAL FIELD

The present invention relates generally to the delivery of therapeuticfluids to a treatment site within a patient. More specifically, theinvention relates to methods and devices for treating tissue within thehuman body using a pressurized injection system that accurately deliverstherapeutic fluids to a desired location, such as the urinary tract of apatient.

BACKGROUND

A wide variety of medical treatments utilize the delivery andintroduction of therapeutic compositions to a treatment location in apatient. In home or outpatient settings, the delivery methods used caninclude procedures such as oral delivery or inhalants, while in clinicalor hospital types of settings, a therapeutic fluid is often injectedusing a needle-based system. In more complicated methods, a fluid can bedelivered surgically through a tubular device, such as a catheter orendoscope, and in some cases, the surgical method can involve minimallyinvasive procedures.

For minimally invasive procedures, a number of systems have beendeveloped for delivering therapeutic fluids to treatment sites within apatient that include minimally invasive, tubular delivery lumens (e.g.,catheters or endoscopes) and pressurized fluid sources. In some cases,these fluid sources include a syringe-like structure that is actuated bya plunger. This plunger can be controlled via a console having controlfeatures that help the user to control the amount of pressurized fluidthat is delivered to and/or expelled from the system. These systems caninclude needleless fluid injection systems, for example. Needlelessdevices and methods for treating tissue of the urinary tract arediscussed, for example, in Applicants' copending application U.S. Ser.No. 12/087,231, filed Jun. 27, 2008 (Copa et al.), titled “Devices,Systems, and Related Methods for Delivery of Fluid to Tissue”, and U.S.Patent Application Publication No. 2006/0129125 (Copa et al.), theentire disclosures of which are incorporated herein by reference. Onearea of the body in which such needleless fluid delivery systems havebeen known to be used is for diseases of the prostate, such asprostatitis, benign prostatic hyperplasia, and prostatic carcinoma.

Needleless fluid delivery systems can include the use of a tube-likedevice, such as an elongated catheter tube, which is configured toprovide a jet-injection of a therapeutic fluid at a desired treatmentsite. Generally, a needleless injector is used to deliver thetherapeutic fluid that is provided from an external reservoir that islocated at a proximal end of the tube-like device. The actual fluidadministration occurs at a distal end of the tube-like device. Due tothe relatively long travel length of the therapeutic fluid through thetube-like device, an injector must generally be capable of pressurizingthe therapeutic fluid to relatively high pressures.

For any injection or injected tissue, therapeutic agents should bedelivered with minimal discomfort and procedure time, and with the bestpossible degree of accuracy of delivery location and delivery volume,and with uniform and accurate distribution of a fluid throughoutinjected tissue. Further, due to the characteristics associated with thedelivery of therapeutic compositions to treatment locations in apatient, there is a need to provide improved procedures, systems, andcomponents for fluid delivery using needleless fluid delivery systems.Such procedures, systems, and components would provide for accurate andcontrolled dispensing of therapeutic compositions to specific treatmentlocations within a patient. In particular, there exists a continuingneed to provide improved devices for delivering therapeutic fluids todifferent tissues such as locations of the urinary tract including thebladder, bladder neck, prostate, urethra, kidneys, and ureters.

SUMMARY

The invention generally involves needleless fluid injection devices,systems, and methods. These devices and systems allow for targeteddelivery of therapeutic fluids at desired anatomical tissue locations,such as locations in the male or female urinary tract, (e.g., bladder,bladder neck, kidney, ureters, urethra, prostate, etc.). The therapeuticfluids can include biologically active species and agents such aschemical and biochemical agents, for example. Exemplary devices can bedesigned to deliver fluid at various tissue locations, and can furtherdeliver multiple different therapeutic fluids having varying materialproperties (e.g., viscosity). The devices can be capable of deliveringprecise amounts of fluid for injection at precise locations and atspecific pressures that are adjustable depending on the fluid beingadministered to the location in the patient.

In one aspect of this invention, control systems are provided forcontrolling the inflation of a tissue tensioner or balloon for a fluiddelivery system, such as for a needleless fluid injection device. Inanother aspect of the invention, a system for reducing the response timefor jet injection of fluid is provided. In yet another aspect of theinvention, systems and devices are provided for controlling the volumeof fluid that is ejected from a fluid injection system, which systemsinclude at least one stop that is selectively rotated to limit themovement of a shaft in a linear direction, thereby controlling theamount of fluid that is ejected from the system.

In another aspect of the invention, a fluid injection system isprovided, which comprises a shaft comprising a proximal end, a distalend, and at least one protrusion extending from an outer surface of theshaft adjacent the proximal end, and a rotatable, stepped stop membercomprising multiple flat step portions, wherein the stop member ispositioned concentrically around the shaft, and wherein the shaft islinearly translatable in a distal direction for engagement of the atleast one protrusion with at least one of the flat step portions.

In yet another aspect, a high-pressure fluid injection system isprovided, which comprises a rechargeable injection chamber comprising aproximal end, a distal end, and an internal opening extending from theproximal end to the distal end, a plunger slideably engaged with theinternal opening of the injection chamber, an injection tube extendingfrom the distal end of the injection chamber and in fluidiccommunication with the internal opening of the injection chamber, and acheck valve between the proximal and distal ends of the injectionchamber. The internal opening comprises a high-pressure zone adjacent tothe check valve and having a first diameter, and a low-pressure zoneproximal to the high-pressure zone and having a second diameter that islarger than the first diameter.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be further explained with reference to theappended Figures, wherein like structure is referred to by like numeralsthroughout the several views, and wherein:

FIG. 1 is a schematic illustration of one embodiment of a needlelessfluid delivery system for delivering a therapeutic fluid to a treatmentlocation, in accordance with the invention;

FIG. 2 is a schematic illustration of a control system that can be usedto control inflation of a tissue tensioner or balloon of a fluiddelivery system;

FIG. 3 is a schematic illustration of another control system that can beused to control inflation of a tissue tensioner or balloon of a fluiddelivery system;

FIGS. 4 and 5 are front, partial schematic views of a system forachieving relatively high jet stagnation pressure in a short time for afluid delivery system of the invention;

FIGS. 6-9 are front views of portions of fluid delivery systems of theinvention, which include devices for controlling the volume of fluidthat is ejected from the delivery systems;

FIG. 10 is a front view of a high-pressure fluid injection systemincluding a rechargeable injection chamber including a check valve; and

FIG. 11 is a front view of a portion of a high-pressure fluid deliverysystem having stepped dosage control.

DETAILED DESCRIPTION

The invention relates to devices and methods useful for injecting fluidinto tissue for treatment. The fluid can be injected without the use ofa needle and can therefore be referred to as a needleless fluidinjection system. Needleless fluid injection systems of the inventioncan include one or more orifices that deliver fluid in the form of astream of fluid, which may be referred to as a jet or fluid stream, at apressure, velocity, and stream size that allow the fluid stream to passthrough a tissue surface, penetrate into the bulk of the tissue belowthe tissue surface, and become dispersed as fluid particles within thetissue, such as in the form of a cloud of dispersed fluid particles ordroplets, without a needle structure passing into the tissue. The typeof tissue injected for treatment can be any amenable tissue, which caninclude tissue at or near the urinary tract (e.g., tissue of theprostate, kidneys, ureters, urethral tissue, bladder (including thebladder neck), etc.), or other tissues such as heart tissue, as desired.

Needleless devices of the type described herein generally include adistal end and a proximal end. As used herein, a “distal end” of adevice or system refers to an end area or portion of the device orsystem that can be introduced internally within a patient's body duringa treatment procedure, generally including the distal end of an elongateshaft or catheter tube. For example, an elongate shaft or catheter ofthe needleless injection systems of the invention generally includes adistal end that is the first portion of the device that is introducedinto the patient for treatment. A distal end may include functionalfeatures that operate on fluid or tissue during use, such as one or moreejection orifices, delivery heads (e.g., end effectors, nozzles, etc.)that house one or more ejection orifices, a frictional tissue holdingtip, tissue tensioners, lighting or other optical features, steeringfeatures, and the like.

As used herein, a “proximal end” of an exemplary needleless device orsystem is the end that is opposite the distal end of that device orsystem. To that end, each individual component of a system can includeits own proximal and distal ends, while the overall system can alsoinclude proximal and distal ends. For one example, a needleless fluidinjection system of the invention can include an injector body orconsole at a proximal end that remains external to the patient duringuse and an elongate shaft or catheter tube at a distal end. That is,exemplary needleless fluid delivery devices or systems can include aproximal end that includes a console, and an elongate shaft extendingfrom a proximal end, which is in communication with the console, to adistal end. One or more injection orifices at the distal end can be influid communication with the console.

An exemplary console used with systems of the invention can include ahousing that connects to or is otherwise (directly or indirectly) influid communication with an elongate shaft or catheter tube. The consolecan include fluid that can be pressurized by a pressure source to causethe fluid to flow through the shaft for injection into tissue at thedistal end. A device can eject fluid from one or multiple ejectionorifices that can be located at the distal end of the shaft or cathetertube

A device can eject fluid from at least one injection orifice located atthe distal end of the shaft. Optionally, multiple injection orifices maybe located at one or more locations along a length of or about acircumference of a shaft distal end. Devices, systems, and methods aredescribed herein that can be used to inject a fluid through a surface ofa tissue, penetrating without the use of a needle through the tissuesurface and into the bulk of the tissue, and dispersing as particles ordroplets within the tissue below the tissue surface. The injected fluidsmay be referred to as an “injectate” or “injection fluid”, which may beany type of fluid such as a therapeutic fluid. The injectate can beadministered into tissue in a needleless manner, whereby the injectateis delivered as a pressurized fluid stream or jet. This contrasts withinjections performed using a needle, whereby a hollow needle structurepenetrates tissue to locate a hollow end of the needle within a tissuemass, below the tissue surface, after which the needle carries fluidinto the bulk of the tissue and delivers the fluid at a relatively lowpressure to the tissue in the form of a body or pool of fluid known as abolus.

Referring now to the Figures, wherein the components are labeled withlike numerals throughout the several Figures, and initially to FIG. 1,one preferred configuration of a needleless fluid delivery system 100 isschematically illustrated. Delivery system 100 generally includes aninjection console 102, an injection chamber 108 in operativecommunication with the console 102, and a catheter tube or elongateshaft 104 that is also in operative communication with the console 102.The console 102 includes a user interface 106, which can be used foractivating and controlling the activities of the various components ofthe delivery system 100. The user interface 106 can include an inputmeans for selectively delivering a volume of pressurized fluid throughthe injection chamber 108. The user interface 106 may further includeone or more actuatable devices, such as a foot petal, a hand activatedcontroller, switches, buttons, and/or the like. It is also contemplatedthat the user interface 106 can include a touch-screen that is capableof receiving touch commands and may optionally include a display systemfor displaying information such as the mode of operation that is beingused and/or certain operating parameters of the system.

Although console 108 can include a wide variety of features, any consoleused in the fluid delivery systems of the invention can generallyinclude a housing, a pressure chamber, and a pressure source. A consolecan have any configuration, size, or design, ranging from a small,hand-held design to a relatively larger floor or table-mounted console.The consoles can also include separate or separable components such as apressure chamber or injection chamber that can be attached, used for aninjection procedure, and detached and optionally discarded or sterilizedand reused. A shaft or catheter tube can also be attached to a consoleor a pressure chamber in a manner that facilitates separation andoptional re-attachment or disposal.

With separable components, a shaft or injection chamber can be attachedto a console housing and used to inject a first patient and/or a firstinjectate, and then the shaft or pressure chamber can be removed anddiscarded or sterilized. A second shaft or pressure chamber can then beattached to the console to treat a second patient or the first patientwith second injectate or administer another treatment of the firstinjectate. The second patient or injectate can involve injection andtreatment of the same type of tissue as the first patient or injectate,or of a new type of tissue than was treated in the first treatment. Inthis manner, separable and optionally disposable shaft or pressurechamber components of a needleless injection system can allow a consolehousing to be used multiple times to inject the same or differentinjectates to the same or different patients, and to the same ordifferent types of body tissue, thereby providing an injection systemthat is flexible for use in a wide variety of situations and with a widevariety of fluids. Examples of system configurations, features andcombinations of system features that can be useful according to thepresent description include U.S. Patent Application Publication No.2006/0129125 (Copa et al.); U.S. Publication No. 2009/0312696, filedJun. 27, 2008 (Copa et al.); PCT patent application Serial No.US09/06390, filed Dec. 4, 2009 (Crank et al.), titled “Devices, Systems,and Related Methods for Delivery of Fluid to Tissue”; PCT patentapplication Serial No. US09/06384, filed Dec. 4, 2009 (Crank), titled“Needleless Injection Device Components, Systems, and Methods”; PCTpatent application Serial No. US09/06383, filed Dec. 4, 2009 (Rykhus etal.), titled “Method and Apparatus for Compensating for Injection MediaViscosity in a Pressurized Drug Injection System”, the entireties ofwhich are all incorporated herein by reference.

A console can include actuating features to control distal end features,e.g., for steering a steerable distal end of a steerable shaft, toactuate ejection of fluid, to move a moveable or extendable injectionshaft or one or more injection orifice relative to another shaftcomponent such as a working shaft, optional ports to connect a consolehousing to auxiliary devices, electronics such as controls, opticfeatures such as a lens, fiber optic, or electronic viewing mechanism toallow viewing through an optical feature (to view a location ofdelivery), and an actuating mechanism or pressure source for a tissuetensioner in the form of a mechanical tissue tensioner or an inflatableballoon. One or more attachment ports can optionally attach a console toan external and optionally remote component such as an external orremote pressure source, vacuum source, or an external or remote fluidreservoir to supply injectate or other fluid, such as to inflate aballoon. For example, a console (e.g., console housing or connectormember) may have a fluid port that attaches to a source of a fluid tosupply the fluid to the console, such as to a permanent or detachablepressure chamber. Embodiments of consoles can include a permanent orremovable pressure chamber and a pressure source capable of pressurizinga fluid contained in the pressure chamber to cause the fluid to flowfrom the console, through a lumen in the shaft, and then through aninjection orifice.

In embodiments of devices that involve the use of a control fluid, apressurized control fluid can be produced by a console using any usefultechnique and mechanism. For example, the pressurized control fluid canbe produced by a pressure source, such as any pressurized fluid source,magnetohydrodynamic power, expanding steam or gas power, or the like,with any available and useful control fluid, which may be a liquid or agas.

Fluid can be provided to the system 100 by a fluid supply 110, which canbe provided as a syringe that is manually activated, such as byphysically pressing a plunger into a syringe barrel that is at leastpartially filled with fluid to push fluid from the syringe barrel.Alternatively, fluid supply 110 can have a different configuration thana syringe, and the fluid supply can be automatically or mechanicallyactivated, such as with an electronic fluid supply controller or withone or more remote activation devices that can be manipulated by theuser to move the plunger into and out of a syringe barrel. In yetanother alternative, the fluid supply 110 is not a syringe, but insteadincludes a larger fluid source, such as a reservoir or other containerthat holds the fluid until it is provided to the injection chamber 108.Such a container can be positioned so that the fluid is gravity fed tothe injection chamber, for example, or so that the fluid can beextracted using a vacuum source, for another example. With any of thedifferent types of fluid supplies used with the systems of theinvention, it is contemplated that an exact amount of fluid to beadministered can be premeasured and provided to the system until thatquantity of fluid is depleted and/or a predetermined amount of fluid canbe extracted from a relatively large fluid supply.

A fluid chamber can be a space or volume at a proximal end of a device,such as at a console housing, which can be used to contain pressurizedor non-pressurized fluid (e.g., control fluid or injectate). Examples ofspecific types of fluid chambers include fluid reservoirs and pressurechambers. Optionally, a proximal end of a device may include one ormultiple fluid reservoirs and pressure chambers, which can be providedfor one or more different fluids including one or more injectates, oneor more control fluids, or combinations of injectates and controlfluids.

A fluid reservoir is generally a type of fluid chamber that can containa fluid for a purpose of containing, transferring, holding, or storing afluid, such as a fixed volume fluid chamber, and may be included as apermanent or removable (i.e., attachable and detachable) component of aconsole housing.

A pressure chamber or injection chamber can be a type of fluid chamberfor containing one or more fluids (e.g., control fluid or injectate) fora purpose of placing the fluid under pressure to deliver the fluidthrough a lumen to a distal end of a shaft for ejection from an ejectionorifice. Examples of pressure chambers include a syringe chamber andother variable volume spaces that can be used to contain and pressurizea fluid. Examples of variable volume pressure chambers include spacesthat can exhibit a variable volume for increasing or decreasing thevolume (and correspondingly decreasing or increasing pressure) withinthe variable volume chamber space. Such pressure chambers can include aplunger, piston, bellows, or other mechanisms. A pressure chamber can bepressurized by a pressure source attached to the plunger, bellows, orpiston, etc., such that fluid contained in the pressure chamber isejected under pressure. This pressurized fluid can be used for priming adevice and/or for ejecting fluid from an ejection orifice for injectionand/or to produce a control force, for example. A pressure source may beany source of energy (e.g., mechanical, electrical, hydraulicallyderived, pneumatically derived, or the like) such as a spring, solenoid,compressed air, manual syringe, electric power, hydraulic, pneumaticpressure sources, or the like. A pressure chamber may be a permanent orremovable (i.e., attachable and detachable) component of a consolehousing.

Examples of consoles, console features and combinations of consolefeatures that can be useful according to the present description areidentified in Applicants' copending U.S. Patent Application PublicationNo. 2006/0129125; U.S. Patent Publication No. 2009/0312696, filed Jun.27, 2008 (Copa et al.); PCT patent application Serial No US09/06383,filed Dec. 4, 2009 (Rykhus et al.), titled “Method and Apparatus forCompensating for Injection Media Viscosity in a Pressurized DrugInjection System”; and PCT patent application Serial No. US09/06381,filed Dec. 4, 2009 (Crank), titled, “Devices, Systems and Methods forDelivering Fluid to Tissue”, the entire disclosures of which areincorporated herein by reference.

In communication with a proximal end of a device is an elongate shaftthat extends from the proximal end (i.e., from a proximal shaft end),which is optionally removably connected to the console (or a componentof the console such as a removable pressure chamber), to a distal endthat can be placed in a patient during an injection procedure. A shaftcan be of various designs, minimally including an injection lumen tocarry injectate from a proximal end of the device to a distal end of theinjection shaft. Shafts for needleless devices as described are alsodescribed in PCT patent application Serial No. US09/06390, filed Dec. 4,2009 (Crank et al.), titled “Devices, Systems, and Related Methods forDelivery of Fluid to Tissue”; and in PCT patent application Serial No.US09/06384, filed Dec. 4, 2009 (Crank), titled “Needleless InjectionDevice Components, Systems, and Methods”; the entireties of which areboth incorporated herein by reference.

Referring again to FIG. 1, a proximal or supply end 111 of the cathetertube or shaft 104 extends from a distal end of the injection chamber108. The catheter tube 104 may be permanently attached or connected tothe injection chamber 108 so that the tube 104 and chamber 108 areprovided to the system either as a single component. Alternatively,catheter tube 104 may be attachable and detachable from injectionchamber 108, such as with quick connection fittings, so that theinjection chamber 108 and tube 104 are provided to the system asseparate components. Catheter tube 104 further includes a delivery ordistal end 112, which is generally opposite the proximal or supply end111.

Catheter tube or shaft 104 is a generally continuous, elongated tube,which may include multiple lumens, attachments, or other components thatmay extend along all or part of the length of the tube 104. Cathetertube 104 may further comprise a number of different configurations, suchas an endoscope or other catheter configuration, for example.Alternatively, catheter tube 104 can comprise a flexible, elongated tube114 to allow for easy positioning of the delivery or distal end 112within the patient. Supply or proximal end 111 of the tube 104 can begenerally configured to attach to the injection chamber 108 and caninclude a quick-connect style connector. Alternatively, the proximal end111 of the tube 104 can be permanently attached to the injection chamber108.

Referring again to FIG. 1, delivery or distal end 112 of elongated tube104 can comprise a number of different configurations, which can beselected to provide treatment to a certain location in the patient'sbody (e.g., a rectal treatment location, a gastrointestinal treatmentlocation, a nasal treatment location, a bronchial treatment location, oran esophageal treatment location). The configuration of this distal end112 is designed and/or selected to provide different types of treatment,such as can be provided by end-fire applicators or side-fireapplicators.

An injection shaft minimally includes an injection lumen incommunication with an injection orifice. The injection shaft can includestructure such as sidewalls that define the injection lumen, thesidewalls being of sufficient strength to withstand operating pressuressufficient to deliver injectate from the injection orifice at anelevated pressure sufficient to cause the injectate to be ejected fromthe injection orifice to penetrate a tissue surface and become injectedinto and dispersed below the tissue surface. An injection shaft may beof a flexible material (e.g., a metal or polymeric tube) that canwithstand such injection pressure, and may be prepared from exemplarymaterials capable of withstanding pressure of an injection, e.g.,Nitinol, stainless steel, reinforced (e.g., braided) polymer, as alsodescribed elsewhere herein.

A basic version of a useful shaft of a device as described can be an“injection shaft” that includes a proximal end, a distal end, a sidewallthat defines an internal lumen (“injection lumen”), and at least oneinjection orifice at the distal end in connection with the injectionlumen.

An injection shaft can be any elongate structure capable of deliveringfluid to a distal end of the injection shaft at a pressure suitable toinject tissue, as described. Exemplary injection shaft structuresinclude relatively flexible hollow bodies having a distal end, aproximal end, sidewalls extending between the ends, and an internallumen defined by interior surfaces of the sidewall. The injection lumenis in communication with one or more injection orifice at the distalend; the injection orifice may be as described herein, such as anaperture or bore in an injection shaft sidewall, an aperture or bore ina nozzle, end effector, injection head, or other structure incommunication with the injection lumen.

An exemplary injection shaft can include a sidewall that defines anouter shaft surface and an inner injector lumen, these being ofcontinuous and relatively uniform dimensions of inner diameter, outerdiameter, and wall thickness, along an entire length of the injectionshaft. Alternately, an injection shaft, injector lumen, or sidewall, maychange dimensions (e.g., wall thickness) along the length of theinjection shaft, with a larger wall thickness (e.g., greater outerdiameter) at a proximal end and a thinner wall thickness (e.g., reducedouter diameter) at the distal end. A length of an injection shaft can beany length that functions to place a proximal end at a console and adistal end at a desired tissue location.

An injection shaft can be a component of a shaft of a needlelessinjection device or system. Other shaft components may includeadditional elongate shaft structures with desired functionality, asingle example being a device referred to herein as “medical deviceshaft” or a “working shaft,” which can be used to securely or moveablysupport or house an injection shaft. For instance, an injection shaftcan be incorporated permanently or movably against or within a workingshaft. In exemplary embodiments an injection shaft can be looselycontained in a working lumen of a working shaft to allow movement of theinjection shaft length-wise and rotationally relative to the workingshaft; an injection shaft may be capable of moving longitudinally withina working lumen to allow the injection lumen to be extended distallyfrom an open end of a working lumen at a distal end of the workingshaft.

An example of a “working shaft” or “medical device shaft” can be a shaftthat is useful in conjunction with an injection shaft, to manipulate andplace the injection orifice of an injection shaft at a desired locationfor treatment of tissue. A “working shaft” or “medical device shaft” canfunction to support the injection shaft and can optionally andpreferably include any of a variety of optional functionalities such assteerability, an optical function, a tissue tensioner, or combinationsof these, in addition to supporting the injection shaft.

An example of a particularly preferred working shaft can includefeatures of a typical cystoscope, endoscope, ureteroscope, choledoscope,hysteroscope, catheter (e.g., urinary catheter), or the like, or othersimilar type of medical device shaft, including one or more feature offlexibility, an optical function, a steerable distal shaft end, and aworking lumen.

A distal end of an injection shaft includes one or multiple injectionorifices for ejecting fluid within a body of a patient. An injectionorifice can be any form of opening, aperture, or orifice, such as anaperture or bore in an injection shaft sidewall, or an aperture or borein a nozzle, end effector, injection head, or other structure incommunication with an injection lumen. Injection orifices can be locatedat relative locations and orientations along a length or circumferenceof an injection shaft distal end to result in ejection and distributionof ejected fluid in different directions (e.g., circumferentiallyrelative to the shaft), optionally or alternately at different distancesalong the length of the injection shaft. An injection orifice can bedirected at any angle relative to a longitudinal axis of a shaft, suchas perpendicular, angled toward a distal end, or angled toward aproximal end.

According to exemplary injection methods and devices, an injectionorifice may be located on a proximal side of a distal end tip at alocation that allows the injection orifice and adjacent injection shaftsidewall to contact a tissue surface as a longitudinal axis of a shaftthat contains the injection orifice is positioned in an orientation thatis parallel to the tissue surface. These device embodiments aresometimes referred to as “side-fire” devices, herein. As used herein, a“distal end tip” can be considered a location of a distal end of aninjection shaft that is the farthest (most distal) feature of theinjection shaft distal end. In certain embodiments of “side-fire”devices an injection orifice can be located a distance away from adistal end tip on a proximal side of the distal end tip so the injectionorifice is located to contact tissue for injection by placing the shaftsidewall in contact with tissue.

According to certain exemplary devices, a distal end of a shaft(injection shaft, working shaft, or the like) can include a tissuetensioner, the tissue tensioner optionally being attached to the distalend of the shaft by a fastener that is attached to the tissue tensioner,such as part of a tissue tensioner assembly. A tissue tensioner can belocated at a distal end of a shaft, somewhat near to an injectionorifice, e.g., to be within a body lumen such as a urethra, e.g., aprostatic urethra, and near the injection orifice when the distal end ofthe shaft is installed in a patient for injection. For example a tissuetensioner can be located at a length-wise location along an injectionshaft that is the same length-wise location as the length-wise locationof an injection orifice.

A tissue tensioner can comprise an expandable surface, e.g., acontinuous expandable surface such as an inflatable balloon, or anon-continuous expandable surface such as an expandable metal (orplastic) cage or the like. The expandable surface can exhibit anexpanded state and a non-expanded state. According to exemplary methods,a tissue tensioner can be placed in a body lumen in a non-expanded stateand expanded within the lumen to the expanded state. In the expandedstate, the tissue tensioner contacts an internal surface of the lumen tohold the distal end of the shaft and an associated injection orifice inplace relative to desired tissue for injection. The tissue tensioner canoptionally produce tension or strain on the tissue in a manner that canaffect the manner in which an injected fluid stream penetrates thetissue surface and becomes distributed in the tissue upon injection. Atissue tensioner can facilitate a good result upon injection of fluidthrough luminal tissue by ensuring that the luminal tissue is fixed andincludes a desired amount of tension for receiving an injection.

Depending on the configuration of an injection orifice at a shaft of adevice, or at an injector head, a tissue tensioner can be used to placea desired portion of tissue in (e.g., direct) contact with an injectionorifice, i.e., a surface that contains an injection orifice.Alternately, a tissue tensioner can place a desired portion of tissue ata desired distance away from an injection orifice, e.g., in the instanceof an injector head that includes two surfaces with a recessed surfaceincluding an injection orifice. The distance, if any, between aninjection orifice and tissue, at injection, can be selected to affectproperties of the injection, e.g., to affect the distance an injectatepenetrates into tissue, the size of droplets formed beneath the tissuesurface, and the pattern over which droplets of injectate are dispersedthroughout tissue when injected. Other factors can also be adjusted toaffect properties of the injection such as pressure and volume ofinjectate, size and shape of the injection orifice, etc.

Examples of tissue tensioners include inflatable balloons located at ashaft distal end near an injection orifice (e.g., at the samelength-wise location as the injection orifice), and mechanicallyextendable structures such as paddles, protrusions, levers, metal orplastic cages, metal or plastic springs or spirals, and the like, any ofwhich can include a surface that can be extended (e.g., mechanically)from a distal end of a working shaft or injection shaft to placepressure on internal tissue, e.g., on urethral tissue within theprostatic urethra or other luminal tissue. Tissue tensioners, deviceshafts, and related mechanisms and methods are described in Applicants'copending U.S. Patent Publication. No. 2006-0129125, and U.S. PatentPublication No. 2009-0312696, the entireties of which are bothincorporated herein by reference.

A balloon or a mechanically extendable tissue tensioner can be inflatedor extended at a location that is approximately at a length along adistal end of a shaft that is near an injection orifice, e.g., at alength-wise location that is the same as the length-wise location of theinjection orifice. When used within a lumen such as a urethra, thetissue tensioner can push luminal tissue (e.g., urethral tissue) awayfrom the distal end of the shaft in a manner that causes the luminaltissue and an injection orifice to contact each other. This can be done,for example, by a balloon expanding from an opposite side of a shaftrelative to an injection orifice to place pressure on luminal tissuelocated opposite from an injection orifice and to cause the injectionorifice to contact adjacent luminal tissue, optionally to producepressure, strain, or tension on the luminal tissue opposite of theballoon. A mechanical tensioner may be extended from a distal end of ashaft by use of an actuating mechanism such as a mechanical connectionbetween the tissue tensioner and the proximal end of a device, such asat a working shaft proximal end. An inflatable balloon may be extendedfrom a distal end of a shaft by inflating the balloon with pressurizedfluid such as liquid, air, other gaseous fluids, or the like.

A number of different techniques and control systems can be used toinflate a balloon that is being used as a tensioner, as describedherein. One exemplary system is illustrated in FIG. 2 and involves anautomatic balloon inflation control system that provides for automatedinflation based on volume control. In particular, this system includesan input tube or structure 150, a regulator 152, a first automatic valveor powered valve (e.g., a solenoid valve) 154, an adjustable valve 156,a second automatic valve (e.g., an automated pneumatic valve) or poweredvalve 158, and an output tube or structure 160. In operation, a materialsuch as liquid, air, or gas is provided to the input structure 150, withthe intention that this air or gas will be regulated by the controlsystem to provide the desired inflation of the balloon or tensioner,which is operationally attached to the output structure 160. In onemethod, the steps include placing the first valve 154 in an openposition and the second valve 158 in an open position to inflate theballoon. When the desired amount of air or gas has been transferred tothe balloon, the first valve 154 will be closed. When it is desired todeflate the balloon, the second valve 158 will then vent to allow theballoon to deflate. These steps can be repeated to inflate and deflatethe balloon, as desired.

The two-valve system of the type illustrated in FIG. 2 includes a firstvalve, which is either open or closed in both directions in its twopositions. Another, second valve is either open or venting thedownstream side to the atmosphere while the upstream side is closing. Inthis way, the first valve functions to allow flow in or to hold pressureback and the second valve functions to allow flow in or vent downstream(i.e., balloon) pressure while holding back upstream flow. Thisarrangement of valves is advantageous because it is capable of holdingback upstream flow, allowing flow, holding downstream pressure, andventing the downstream pressure as desired for inflation and deflationof a balloon.

With this method, the total volume of gas or air that flows to theballoon is controllable by controlling the flow rate with the regulator152 and/or the adjustable valve 156 and the corresponding time that thegas or air is allowed to flow to the balloon. This is performed duringthe duration of the step that involves having the first and secondvalves 154, 158 in their open positions.

Although the system described relative to FIG. 2 includes a regulator,two valves or automatic valves, and an adjustable valve, it isunderstood that the system can instead include only two of thesecomponents, depending on certain system parameters. Depending on theconsistency of the supply pressure, exemplary combinations of thecomponents include the following: (1) a regulator, an adjustable valve,and two 2-position valves; (2) a regulator, an adjustable valve, and one3-position valve; (3) a regulator and a 3-position valve; (4) aregulator and two 2-position valves; (5) an adjustable valve and a3-position valve (for a constant supply pressure); (6) an adjustablevalve and two 2-position valves (for a constant supply pressure); (7)one 3-position valve (for a constant supply pressure); and (8) two2-position valves (for a constant supply pressure). The adjustableparameter in these configurations is the time that the fluid path isopen.

Another exemplary system that can be used to inflate a balloon that isbeing used as a tensioner is illustrated in FIG. 3 and involves anautomatic balloon inflation control system that provides for automatedinflation based on pressure control. In particular, this system includesan input tube or structure 170, a regulator 172, an automatic valve(e.g., an automated pneumatic valve) or solenoid 174, and an output tubeor structure 176. In operation, a material such as fluid, air, or gas isprovided to the input structure 170, with the intention that this air orgas will be regulated by the control system to provide the desiredinflation of the balloon or tensioner, which is operationally attachedto the output structure 176. In one method, the steps include moving thevalve 174 from its closed position to its open position, allowing theballoon to be pressurized by the fluid to a pressure controlled by theregulator 172. When it is desired to deflate the balloon, the valve 174will then vent, which can be accomplished, for example, with a2-position valve that blocks the upstream flow and vents the downstreampressure in one position, and that allows flow from upstream todownstream in another position. These steps can be repeated to inflateand deflate the balloon, as desired. Thus, this system uses theregulator 172 to control the pressure transmitted to the balloon.

When using the various devices of the system to inject pressurized fluidinto tissue, it can be advantageous to get the fluid or “jet” up to adesired operational speed quickly. In this way, a larger amount of thefluid dose can be ejected at a speed that is sufficient to penetrate thetarget tissue. This can be particularly beneficial when administeringrelatively small doses of the fluid. To that end, FIGS. 4 and 5illustrate a device and method for achieving a higher jet stagnationpressure in less time in order to have better fluid penetration in thetarget tissue. In particular, FIG. 4 illustrates an air or gas cylinder200 that drives the fluid injection. Cylinder 200 includes an outercylindrical wall 202 and a plunger 204. FIG. 5 illustrates this cylinder200 in combination with a regulator 210, a reservoir 212, which maycontain a volume of compressed air or gas, and a valve 214. The valve214 controls the flow of fluid to the firing/injection side of thecylinder 200. In order to achieve a faster response time for the jet,the side of the cylinder 200 that does not drive the injection ispressurized, to return the cylinder 200 to its starting position, atwhich point it can be vented. The reservoir 212 of compressed air orgas, which is positioned just upstream of the valve 214, provides animpulsive force for quick acceleration upon opening of the upstreamvalve 214. In general, increasing the product of pressure and volumeupstream from the regulator 210 will also reduce jet response time togive faster flow acceleration.

An alternate way of accomplishing the quick acceleration of a fluid jetis to use gas power and have a regulator that could modulate theacceleration of the air cylinder. However, this system would requirevery fast response times in the control of the regulator.

An exemplary embodiment of a high-pressure fluid injection system 250including a rechargeable injection chamber 252 with a check valve 260 isillustrated in FIG. 10. The injection chamber 252 includes a plunger254, a high-pressure zone 256, a low-pressure zone 258, the check valve260, and one or more seals 262, 263 in operative engagement with theplunger 254. In particular, seal 262 can be considered to be ahigh-pressure seal, while seal 263 can be considered to be a relativelylow-pressure seal. When the system 250 includes a check valve 260, asshown, the plunger 254 can advance so that the high-pressure seal 262engages with the high-pressure zone 256. This causes the check valve 260to open. When the plunger 254 stops its forward movement, the checkvalve 260 closes. When the plunger 254 is retracted, a vacuum is thenpulled in the high-pressure zone 256, which causes the high-pressureseal 262 to disengage from the high-pressure zone 256 and injectate thentraverses from a reservoir 264.

In the above-described embodiment, a check valve 260 is used; however,check valves can be expensive and can increase manufacturing time andcosts. Thus, certain embodiments of system 250 do not require a checkvalve. In one embodiment, the injection chamber can be equipped with aplunger configured to retract relatively quickly in order to reduce thetime allowed for external fluid within the system to be pulled into theinjection chamber. In addition, the size (e.g., small) or shape of thecatheter lumen or tubing and corresponding tip orifices can assist incontrolling fluid flow by providing a level of flow resistance. Thesebeneficial design features of the chamber and lumen configurations canpermit control of the fluid flow without the use of a check valve. Assuch, the steps discussed above that require the opening and closing ofthe check valve 260 are not necessary. In addition, variousconfigurations of the lumen 270, plunger 254, injectate orifices 272,and injection chamber 252 can be included to control the fluid flowwithout the use of the check valve 260.

FIGS. 6-9 illustrate systems and devices for controlling the volume offluid that is ejected from an injection system, in accordance with theinvention. FIG. 6 illustrates a portion of an injection system 300,which generally includes a shaft 302, the movement of which determinesthe volume of fluid that is displaced or ejected from an end 304 of thesystem. This fluid can be provided by a reservoir 330, for example,which can include a syringe or other fluid container. In particular, thedistance that the shaft 302 travels in a linear direction will determinethe volume of fluid that will be ejected from the system. The system 300further includes a rotating, stepped stop member 310 that is positionedgenerally concentrically about the shaft 302. The member 310 is furtherattached at one end to a first gear 312, which in turn is engaged with asecond gear 314. The second gear 314 is operationally attached to amotor 316, which thereby drives the rotational movement of the member310 via its attached gear 312. Alternatively, many different types ofgears could be used in place of those illustrated, along with varioustypes of belts, chains, etc., and combinations thereof, in an automatedsystem. In addition, the rotating stepped stops can be positionedmanually or in an automated manner, as desired.

The member 310 further includes a series of grooves or stops 318 spacedaround its circumference, where each of the grooves or stops 318 isarranged in a step-like or angular configuration, as shown. Further, theend of the shaft 302 that is extendible beyond the member 310 includes ashaft protrusion 320 that is at least long enough to be able to engagewith the grooves or stops 318 when the shaft 302 moves linearly upward(relative to this figure). The protrusion 320 may extend from one orboth sides of the shaft 302, although its engagement with the member 310may be more secure when it protrudes from both sides of the shaft 302than when it protrudes from one side of the shaft. The protrusions 320may be formed by pressing dowel pins or other similar devices through ahole that extends at least partially through the shaft 302.

In operation, fluid is provided to a channel 332 adjacent the end 304 ofthe system from which the fluid will be ejected. The member 310 isrotated either by an automatic system or by manual adjustment to placeit in a desired location that is associated with a certain volume offluid that is intended to be ejected from the end 304. That is, thesystem is configured such that particular positions of the member 310are associated with a particular fluid administration. A force is thenplaced on the shaft 302 at the end closest to the protrusion orprotrusions 320 to move the shaft 302 in a linear direction toward theend 304. Springs, pneumatic cylinders, magnetic forces, and other motiveforces may generate this force. This movement of the shaft 302 willcontinue until one or more protrusions 320 engage with one or morecorresponding grooves or stops 316, thereby preventing any furtherlinear movement of the shaft. In this way, the travel of the shaft iscontrolled, thereby controlling the volume of fluid that is displacedfrom the system.

FIG. 7 illustrates another exemplary embodiment of a system of the typeillustrated in FIG. 6, which includes two rotating, stepped stop members410, 440 which are generally concentrically positioned relative to eachother. The system further includes a shaft 402 with one or moreprotrusions 420 that will be adjacent the members 410, 440. This systemfurther includes two motors 416, 417, wherein the motor 417 rotates themember 410 and the motor 418 rotates the member 440. As with theembodiment of FIG. 6, the shaft protrusion(s) 420 of this embodimentalso are engageable with grooves 416, 422 to control the movement of theshaft 402 in a linear direction, thereby controlling the volume of fluidthat is ejected from the system.

Another exemplary embodiment of a system similar to those discussedabove is a system 500 illustrated in FIG. 8, which includes a shaft 502having a shaft protrusion 520 at one end, and two stepped stop members510, 540 that are positioned generally concentrically relative to eachother and the shaft 502. As shown, the internal member 540 includes aseries of grooves as are generally described above; however, the outermember 510 includes both small grooves 516 and at least one relativelylong or tall groove 518. In this way, the protrusion 520 can engage withthe small grooves 516, when desired, but when it is desired to allowfurther movement of the shaft, the member 540 can be rotated so that theprotrusion 520 can slide into the groove 518 to be able to engage withthe grooves of the internal member 540.

Another exemplary embodiment of a stepped stop arrangement isillustrated in FIG. 9, in which a system 600 includes two stepped stopmembers 604, 608 that are arranged in a series configuration along ashaft 602. The shaft 602 includes two protrusions 606, 610, which arepositioned to engage with grooves 614, 612 of the members 604, 608,respectively.

In general, multiple rotating stepped stops of the types described abovemay be used when positioned concentrically or serially with respect toeach other. The stops may be rotated by a single driving means, wheresome type of engagement selection would be provided (e.g., a two-wayratchet for directional engagement selection), or by separate means. Toprevent both stops from simultaneously acting on the shaft andconflicting with each other when rotating, stepped stop is needed, theother can be rotated to a position such that its corresponding shaftprotrusions will not engage it. Thus, the long slot or groove describedabove relative to FIG. 8 can provide the “step” for which the travel ofthe shaft protrusion is insufficient to reach. The rotating steppedstops can be rotated with electrical motors, pneumatic motors, or byhand, and each modality can use belts and pulleys, chains and sprockets,or gear sets.

Another exemplary embodiment of a stepped stop arrangement isillustrated in FIG. 11. In this embodiment, a system 700 can optimizethe use of the injectate fluid, thereby reducing the amount of injectatefluid that is wasted in an injection lumen and/or other components ofthe system 700. In particular, system 700 includes a shaft 702, themovement of which determines the volume of fluid that is displaced froman end of the system. This fluid can be provided by a reservoir, whichcan include a syringe or other fluid container. The distance that theshaft 702 travels determines the volume of fluid that will be ejectedfrom the system 700. The system 700 further includes a rotating, steppedstop member 710 that is positioned generally concentrically about theshaft 702. The member 710 is further attached at one end to a first gear712, which in turn is engaged with a second gear 714. The second gear isoperationally attached to a motor 716, which thereby drives therotational movement of the stepped member 710 via its attached gear 712.Alternatively, many different types of gears could be used in place ofthose illustrated, along with various types of belts, chains, etc., andcombinations thereof, in an automated system. In addition, the rotatingstepped stops can be positioned manually or in an automated manner, asdesired.

The member 710 includes a series of steps 718 arranged in a step-likeconfiguration and spaced around at least a portion of its circumference.As a part of the system 700, the end of the shaft 702 that extendsbeyond the stepped member 710 includes a shaft protrusion 720 thatextends at least far enough from the outer surface of the shaft 702 thatit can engage with the steps 718 when the shaft 702 moves linearlyupward (with respect to this figure). Although one protrusion is shown,a system 700 may include multiple protrusions 720 extending from one ormore areas around the shaft 702. The protrusions 720 may be formed bypressing dowel pins or other similar devices through a hole that extendsat least partially through the shaft 702.

In operation, fluid is provided to a channel of the system 700 at andend of the shaft 702 that is opposite that end having the protrusions720. The member 710 is rotated either by an automatic system or bymanual adjustment to place it in a desired location that is associatedwith a desired amount of fluid that is to be ejected from the system700. In particular, the system is configured such that the protrusion720 travels forward until it stops against one of the steps 718, thenthe load is removed, allowing the member 710 to rotate to a newposition. Movement to this new or next sequential position (e.g.,higher, in this figure) allows the protrusion 720 to continue travelingupward, which allows more injectate to be ejected without having toretract a distal end of the device (e.g., an injectate shaft, lumen tip,and the like). For one example, the protrusion 720 can be advanced sothat it stops against a step designated by reference number 730 to ejecta certain dosage of fluid. The member 710 can then rotate (with no loadfrom the protrusion) so that the protrusion 720 aligns with a stepdesignated by reference number 732, thereby providing an additionaldosage of injectate. The protrusion 720 can advance even furtherrelative to the steps 718, if desired, in order to eject yet anotherdosage of injectate. In this way, a controlled or predefined applicationand use of fluid dosage is provided.

In embodiments of the member 710, the number, depth, length, etc. of thesteps 718 can be designed and provided to control the amount of fluidreleased per dosage, and can vary widely depending on the particulartreatment and dosage requirements. Further, the number of steps 718 andcorresponding defined dosages can vary in accordance with the particulardesired performance of the system. In addition, it is contemplated thatvarious motors, plungers, and like devices and techniques can be used tofacilitate the rotation and controlled fluid dosage of the system 700.Further, the components of the stepped rotating stop 710 can be inoperative or fluid communication with other components of the system700, including a fluid reservoir or source, plunger, and the like. Inaddition, the injection chamber or reservoir can be charged with thetotal amount of injectate that is to be injected, or it can instead becharged with a limited amount of injectate so that when a predefinedinjectate dose has been ejected, the plunger or source can be retractedand recharged.

Other stepped or controlled dosage devices, structures, and techniquescan be employed with the systems of the invention to achieve theobjective of controlling fluid dosage and minimizing waste of injectatefluid within the system. For example, non-rotating, pre-defined steppingdevices, pre-defined actuators, and the like, can be used with thedevices and systems of the invention.

The present invention has now been described with reference to severalembodiments thereof. The entire disclosure of any patent or patentapplication identified herein is hereby incorporated by reference. Theforegoing detailed description and examples have been given for clarityof understanding only. No unnecessary limitations are to be understoodtherefrom. It will be apparent to those skilled in the art that manychanges can be made in the embodiments described without departing fromthe scope of the invention. Thus, the scope of the present inventionshould not be limited to the structures described herein, but only bythe structures described by the language of the claims and theequivalents of those structures.

1. A fluid injection system comprising: a shaft comprising a proximalend, a distal end, and at least one protrusion extending from an outersurface of the shaft adjacent the proximal end; and a rotatable, steppedstop member comprising multiple flat step portions, wherein the stopmember is positioned concentrically around the shaft, and wherein theshaft is linearly translatable in a distal direction for engagement ofthe at least one protrusion with at least one of the flat step portions.2. The fluid injection system of claim 1, wherein the stepped stopmember is manually rotatable.
 3. The fluid injection system of claim 1,wherein the stepped stop member is automatically rotatable.
 4. The fluidinjection system of claim 3, further comprising a motor operativelyengaged with the stepped stop member to provide its automatic rotation.5. A high-pressure fluid injection system comprising: a rechargeableinjection chamber comprising a proximal end, a distal end, and aninternal opening extending from the proximal end to the distal end; aplunger slideably engaged with the internal opening of the injectionchamber; an injection tube extending from the distal end of theinjection chamber and in fluidic communication with the internal openingof the injection chamber; and a check valve between the proximal anddistal ends of the injection chamber, wherein the internal openingcomprises a high-pressure zone adjacent to the check valve and having afirst diameter, and a low-pressure zone proximal to the high-pressurezone and having a second diameter that is larger than the firstdiameter.
 6. The fluid injection system of claim 5, further comprisingat least one seal operatively engaged with the plunger.
 7. The fluidinjection system of claim 6, wherein the at least one seal comprises alow-pressure sealing member and a high-pressure sealing member that ispositioned closer to a distal end of the plunger than the low-pressuresealing member.
 8. The fluid injection system of claim 5, furthercomprising a reservoir in fluidic communication with the low-pressurezone of the injection chamber.
 9. The fluid injection system of claim 7,wherein the plunger is slideable in a distal direction to causeengagement of the high-pressure sealing member and the high-pressurezone.
 10. The fluid injection system of claim 9, wherein advancement ofthe high-pressure sealing member into the high-pressure zone opens thecheck valve.
 11. A method of injecting fluid, comprising the steps of:providing a high-pressure fluid injection system comprising: arechargeable injection chamber comprising a proximal end, a distal end,and an internal opening extending from the proximal end to the distalend; a plunger slideably engaged with the internal opening of theinjection chamber; first and second sealing members operatively engagedwith the plunger; a tube extending from the distal end of the injectionchamber and in fluidic communication with the internal opening of theinjection chamber; and a check valve between the proximal and distalends of the injection chamber, wherein the internal opening comprises ahigh-pressure zone adjacent to the check valve and having a firstdiameter and a low-pressure zone proximal to the high-pressure zone andhaving a second diameter that is larger than the first diameter; andadvancing the plunger in a distal direction until a first sealing memberengages with the high-pressure zone and the check valve opens.
 12. Themethod of claim 11, further comprising stopping the advancement of theplunger to allow the check valve to close.
 13. The method of claim 12,further comprising retracting the plunger in an opposite direction fromthe plunger advancement to create a vacuum in the high-pressure zone,thereby disengaging the first sealing member from the high-pressurezone.